Elsevier

Cellular Signalling

Volume 7, Issue 8, November 1995, Pages 827-835
Cellular Signalling

General paper
Phospholipid regulation of a cyclic AMP-specific phosphodiesterase (PDE4) from U937 cells

https://doi.org/10.1016/0898-6568(95)02010-1Get rights and content

Abstract

The regulation of phosphodiesterase-4 (PDE4) by various phospholipids was explored using PDE4 partially purified from U937 cells. Preincubation (5 min, 4°C) of the large molecular weight PDE4 denoted “Peak 2 PDE4” with mixed phosphatidic acids (PAs) produced a 2-fold increase in its Vmax without changing its Km (∼2 μM) for cyclic AMP. This “activation” was not limited to PAs with specific fatty acid substituents: Synthetic PAs containing saturated and/or unsaturated fatty acids 16–20 carbons long produced similar effects. Lysophosphatidic acids (LPAs) and phosphatidylserines (PSs) also induced PDE4 activation, whereas phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and diacylglycerol did not. Antibodies to a peptide region near the PDE4 catalytic site specifically inhibited PA-induced activation. The data demonstrate that anionic phospholipids can act as non-essential activators of a leukocyte PDE4, and suggest biochemical crosstalk between phospholipid-dependent and cyclic AMP-dependent signalling pathways in human leukocytes.

References (26)

  • M.A. Giembycz

    Biochem. Pharmacol.

    (1992)
  • S.R. Grewe et al.

    J. Allergy Clin. Immunol.

    (1982)
  • C.A. Hirshman et al.

    J. Allergy Clin. Immunol.

    (1987)
  • J.H. Exton

    J. Biol. Chem.

    (1990)
  • W.H. Moolenaar

    Adv. Can. Res.

    (1991)
  • M.E. DiSanto et al.

    Biochem. Biophys. Res. Commun.

    (1993)
  • S.L. Macaulay et al.

    Arch. Biochem. Biophys.

    (1983)
  • D.J. Wolff et al.

    Arch. Biochem. Biophys.

    (1976)
  • C. Sette et al.

    J. Biol. Chem.

    (1994)
  • L. Valette et al.

    Biochem. Biophys. Res. Commun.

    (1990)
  • M.E. DiSanto et al.

    Eur. J. Pharmacol.

    (1995)
  • S.L.C. Jin et al.

    J. Biol. Chem.

    (1992)
  • J.A. Beavo et al.

    Mol. Pharmacol.

    (1994)
  • Cited by (10)

    • 2,1,3-Benzothiadiazine derivatives: Synthesis and screening versus PDE4 enzyme

      2005, Farmaco
      Citation Excerpt :

      Chemical, physical and spectroscopic data of already known intermediates (30, 32–39, 41 and 44) [24,38–41] and final compounds (3, 4, 7, 9, 10, 12, 24, 25, 27 and 29) [24,26,42,43] are in agreement with those reported in literature. All compounds were tested at 100 μM concentration for their ability to inhibit the activity of PDE4 extracted from U937 cellular line [44–46]. Also the BTDs previously showing activity on human recombinant enzyme PDE4D3 from Baculovirus/Sf21 insect cell system (3, 4 and 7) [24] and others related compounds (9, 10, 12, 24, 25, 27 and 29) previously synthesized and characterized by antiviral properties [26,42,43], were tested using rolipram as reference compound (Table 1).

    View all citing articles on Scopus
    View full text